Chasing the genes that control resistance to gastrointestinal nematodes

The host-protective immune response to infection with gastrointestinal (GI) nematodes involves a range of interacting processes that begin with recognition of the parasite’s antigens and culminate in an inflammatory reaction in the intestinal mucosa. Precisely which immune effectors are responsible for the loss of specific worms is still not known although many candidate effectors have beenproposed. However, it is now clear that many different genes regulate the response and that differences between hosts (fast or strong versus slow or weak responses) can be explained by allelic variation in crucial genes associated with the gene cascade that accompanies the immune response and/or genes encoding constitutively expressed receptor/signalling molecules. Major histocompatibility complex (MHC) genes have been recognized for some time as decisive in controlling immunity, and evidence that non-MHC genes are equally, if not more important in this respect has also been available for two decades. Nevertheless, whilst the former have been mapped in mice, only two candidate loci have been proposed for non-MHC genes and relatively little is known about their roles. Now, with the availability of microsatellite markers, it is possible to exploit linkage mapping techniques to identify quantitative trait loci (QTL) responsible for resistance to GI nematodes. Four QTL for resistance to Heligmosomoides polygyrus, and additional QTL affecting faecal egg production by the worms and the accompanying immune responses, have been identified. Fine mapping and eventually the identification of the genes (and their alleles) underlying QTL for resistance/susceptibility will permit informed searches for homologues in domestic animals, and human beings, through comparative genomic maps. This information in turn will facilitate targeted breeding to improve resistance in domestic animals and, in human beings, focused application of treatment and control strategies for GI nematodes

Are patients in heart failure trials representative of primary care populations? A systematic review.

BACKGROUND: Guidelines recommend drug treatment for patients with heart failure with a reduced ejection fraction (HFrEF), however the evidence for benefit in patients with mild disease, such as most in primary care, is uncertain. Importantly, drugs commonly used in heart failure account for one in seven of emergency admissions for adverse drug reactions. AIM: To determine to what extent patients included in studies of heart failure treatment with beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and aldosterone antagonists were representative of a typical primary care population with HFrEF in England. DESIGN & SETTING: Systematic review of randomised controlled trials (RCTs) of drug treatment in patients with HFrEF. METHOD: MEDLINE, MEDLINE In-Process, EMBASE, and CENTRAL were searched from inception to March 2015. The characteristics of the patient's New York Heart Association (NYHA) classification were compared with a primary care reference population with HFrEF. RESULTS: Of the 30 studies included, two had incomplete data. None had a close match (defined as ≤10% deviation from reference study) for NYHA class I disease; 5/28 were a close match for NYHA class II; 5/28 for NYHA class III; and 18/28 for NYHA class IV. In general, pre-existing cardiovascular conditions, risk factors, and comorbidities were representative of the reference population. CONCLUSION: Patients recruited to studies typically had more severe heart failure than the reference primary care population. When evidence from sicker patients is generalised to less sick people, there is increased uncertainty about benefit and also a risk of harm from overtreatment. More evidence is needed on the effectiveness of treatment of heart failure in asymptomatic patients with NYHA class I

Quantify the monthly to decadal variability of climate effects on the lower trophic levelse of shelf sea ecosystems

ECOOP WP10, Deliverable no: D10.1.2.1This report describes three studies using multi-decadal simulations of regional coupled hydrodynamics ecosystem models. These models are used to investigate the relationship between lower trophic level marine ecosystems and biogeochemistry, and the physical environment. The models considered here: POLCOMS-ERSEM Atlantic Margin Model run from 1960 to 2003 (NERC and PML) NORWECOM North Sea Model run from 1985-2006 (IMR) ECOSMO (UiB-GFI) North sea and Baltic Sea run 1980-2004 (UiB-GFI) The POLCOMS-ERSEM model is validated using in-situ data from the world ocean data centre and analysed to investigate the potential long term changes in primary production across the period 1960-2004, in the context of model open boundary conditions and drift. The model experiments demonstrate a strong sensitivity of the on-shelf primary production to the oceanic nutrient boundary conditions, suggesting cross-shelf edge nutrient fluxes provide a significant source of variability. The relationship between the model results and the North Atlantic Oscillation are also considered, demonstrating a r~0.65 correlation with on-shelf nutrients and the NAO The NORWECOM model is validated here using time series data from the Dutch coast. Correlations between model variables in a selection of ICES boxes are compared with a number of driving factors. River loads are shown to dominate coastal boxes. The relationships in open-shelf boxes are more ambiguous, although the southerly inflow is demonstrated to have an important role. The validation of the POLCOMS-ERSEM and NORWECOM models both conclude that the simulations have better skill for nutrients than chlorophyll and in open-shelf seas away from the coast. The validation of ECOSMO presented here focuses on zooplankton and comparison with data from the continuous plankton recorder, investigating six different approaches to matching CPR records with model data. Across the North Sea the mean annual cycle shows good agreement between model and CPR. There is also good correlation with along-track variability. EOF and correlation analysis is used to relate the primary production in the North Sea to atmospheric forcing parameters. The EOF patterns tend to match the distribution of summer time stratification, while the wind speed is shows the highest correlation, particularly during the onset and breakdown of stratification. This indicates the strength of cross-thermocline mixing is an important control on primary production variability. The ECOSMO model has been further developed for use in the Baltic by inclusion of nitrogen fixing cyanobacteria. These studies each demonstrate significant control of the inter-annual variability of shelf sea ecosystems through a range of external forcing vectors: oceanic through cross-shelf edge nutrient flux, terrestrial through variations in river nutrient loading, and atmospheric via the wind control of vertical mixing. Each of these vectors potentially mediates climatic variability and climate change

Interactions involving intestinal nematodes of rodents: experimental and field studies

Multiple species infections with parasitic helminths, including nematodes, are common in wild rodent populations. In this paper we first define different types of associations and review experimental evidence for different categories of interactions. We conclude that whilst laboratory experiments have demonstrated unequivocally that both synergistic and antagonistic interactions involving nematodes exist, field work utilizing wild rodents has generally led to the conclusion that interactions between nematode species play no, or at most a minor, role in shaping helminth component communities. Nevertheless, we emphasize that analysis of interactions between parasites in laboratory systems has been fruitful, has made a fundamental contribution to our understanding of the mechanisms underlying host-protective intestinal immune responses,and has provided a rationale for studies on polyparasitism in human beings and domestic animals. Finally, we consider the practical implications for transmission of zoonotic diseases to human communities and to their domestic animals, and we identify the questions that merit research priority

Carbon on the Northwest European Shelf: Contemporary Budget and Future Influences

A carbon budget for the northwest European continental shelf seas (NWES) was synthesized using available estimates for coastal, pelagic and benthic carbon stocks and flows. Key uncertainties were identified and the effect of future impacts on the carbon budget were assessed. The water of the shelf seas contains between 210 and 230 Tmol of carbon and absorbs between 1.3 and 3.3 Tmol from the atmosphere annually. Off-shelf transport and burial in the sediments account for 60–100 and 0–40% of carbon outputs from the NWES, respectively. Both of these fluxes remain poorly constrained by observations and resolving their magnitudes and relative importance is a key research priority. Pelagic and benthic carbon stocks are dominated by inorganic carbon. Shelf sediments contain the largest stock of carbon, with between 520 and 1600 Tmol stored in the top 0.1 m of the sea bed. Coastal habitats such as salt marshes and mud flats contain large amounts of carbon per unit area but their total carbon stocks are small compared to pelagic and benthic stocks due to their smaller spatial extent. The large pelagic stock of carbon will continue to increase due to the rising concentration of atmospheric CO2, with associated pH decrease. Pelagic carbon stocks and flows are also likely to be significantly affected by increasing acidity and temperature, and circulation changes but the net impact is uncertain. Benthic carbon stocks will be affected by increasing temperature and acidity, and decreasing oxygen concentrations, although the net impact of these interrelated changes on carbon stocks is uncertain and a major knowledge gap. The impact of bottom trawling on benthic carbon stocks is unique amongst the impacts we consider in that it is widespread and also directly manageable, although its net effect on the carbon budget is uncertain. Coastal habitats are vulnerable to sea level rise and are strongly impacted by management decisions. Local, national and regional actions have the potential to protect or enhance carbon storage, but ultimately global governance, via controls on emissions, has the greatest potential to influence the long-term fate of carbon stocks in the northwestern European continental shelf

Heligmosomoides bakeri: a model for exploring the biology and genetics of resistance to chronic gastrointestinal nematode infections

The intestinal nematode Heligmosomoides bakeri has undergone 2 name changes during the last 4 decades. Originally, the name conferred on the organism in the early 20th century was Nematospiroides dubius, but this was dropped in favour of Heligmosomoides polygyrus, and then more recently H. bakeri, to distinguish it from a closely related parasite commonly found in wood mice in Europe. H. bakeri typically causes long-lasting infections in mice and in this respect it has been an invaluable laboratory model of chronic intestinal nematode infections. Resistance to H. bakeri is a dominant trait and is controlled by genes both within and outside the MHC. More recently, a significant QTL has been identified on chromosome 1, although the identity of the underlying genes is not yet known. Other QTL for resistance traits and for the accompanying immune responses were also defined, indicating that resistance to H. bakeri is a highly polygenic phenomenon. Hence marker-assisted breeding programmes aiming to improve resistance to GI nematodes in breeds of domestic livestock will need to be highly selective, focussing on genes that confer the greatest proportion of overall genetic resistance, whilst leaving livestock well-equipped genetically to cope with other types of pathogens and preserving important production traits